Clinical Question

What effect do sodium-glucose cotransporter-2 (SGLT2) inhibitors have on mortality and cardiovascular and renal outcomes in patients with and without diabetes mellitus, heart failure, or kidney disease?

Bottom Line

SGLT2 inhibitors—medications ending in -flozin, such as canagliflozin (Invokana), dapagliflozin (Farxiga), empagliflozin (Jardiance), and ertugliflozin (Steglatro)—reduce all-cause and cardiovascular mortality in patients regardless of the presence of type 2 diabetes, heart failure, or chronic kidney disease. Similar mortality reduction occurs in patients with diabetes regardless of comorbid heart failure, and in patients with heart failure regardless of the presence of diabetes. SGLT2 inhibitors also reduce the progression of renal disease in all patients. (Level of Evidence = 1a–)

Synopsis

Two researchers independently searched three databases, including Cochrane CENTRAL, with the bibliographies of identified studies and abstracts of major cardiology meetings, to identify randomized studies in any language that evaluated the impact of treatment with an SGLT2 inhibitor in patients with or without heart failure or type 2 diabetes. Two researchers independently abstracted the data. The researchers followed PRISMA guidelines and assessed the quality of evidence. They included eight studies of 59,747 patients, comprising three studies that included patients without diabetes. Treatment with an SGLT2 inhibitor reduced the risk of mortality due to all causes (hazard ratio [HR] = 0.84; 95% CI, 0.78 to 0.91), cardiovascular mortality (HR = 0.84; 95% CI, 0.76 to 0.93), and hospitalization for heart failure (HR = 0.69; 95% CI, 0.64 to 0.74) compared with placebo, and reduced a composite of end-stage kidney disease, a doubling of the serum creatinine level, and kidney-related mortality (HR = 0.62; 95% CI, 0.56 to 0.70). There were similar mortality and renal benefits for patients with or without diabetes and patients with or without heart failure. Heterogeneity among study results was moderate for mortality outcomes and low for heart failure hospitalization and kidney outcomes.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Self-funded or unfunded

Setting: Various (meta-analysis)

Reference: Salah HM, Al'Aref SJ, Khan MS, et al. Effect of sodium-glucose cotransporter 2 inhibitors on cardiovascular and kidney outcomes–systematic review and meta-analysis of randomized placebo-controlled trials. Am Heart J. 2020;232:10–22.

Editor's Note: Dr. Shaughnessy is an assistant medical editor for AFP.